Brain water motion, which can be detected by MR techniques, varies depending on many factors, some characteristic of normal physiology and others of pathology. As a result, diffusion weighted imaging is used widely for the evaluation of a number of CNS states. Maintenance of water motion is either itself important for normal brain function or is at least an excellent marker of physiologic state. The Neil/Ackerman laboratory's research program focuses on elucidating the factors which determine water motion. This proposal focuses on learning more about the contribution of extracellular water to the total (intra- plus extracellular) water ADC. Motion in the interstitial fluid has contributions from bulk cerebrospinal fluid (CSF) flow, compartmental boundaries, and Brownian motion. Experiments were designed to determine the relative contribution of these three factors to ADC. The interstitial water ADC will be measured indirectly by measuring the motion of a broad range of extracellular markers. Recent results show that ADCs of compounds confined to the extracellular space are approximately equal despite marked differences in molecular weight (MW). This suggests that bulk CSF flow is a dominating factor. This idea will be tested with both large extracellular markers (polyethyleneglycols of MW=0.9 and 4 kD) and one very small marker (sodium, MW=23). Finally, CSF flow will be pharmacologically altered to directly assess its effect on extracellular water ADC.